SNARE-mediated perforin and cytokine release in natural killer cells. Cytotoxic cells release toxic granules and cytokine messengers to kill pathogen infected and cancerous cells and to mount immune responses. This project will investigate different SNARE molecules that regulate the secretion of perforin from granules and cytokines from other carriers, assisting in the understanding of complex but essential cellular pathways.
Cholesterol and Hydroxycholesterol Shaping Phagocytosis. Reports now show that membrane cholesterol and 25-hydroxycholesterol (25HC) are required for immune cells to ingest and kill pathogens by phagocytosis. This project will measure phagocytosis in macrophages with genetically or pharmacologically varied cholesterol and 25HC, to compare and quantify the ingestion of different bacteria, fungi and particles. This project will also address the link between cholesterol synthesis, its storage in li ....Cholesterol and Hydroxycholesterol Shaping Phagocytosis. Reports now show that membrane cholesterol and 25-hydroxycholesterol (25HC) are required for immune cells to ingest and kill pathogens by phagocytosis. This project will measure phagocytosis in macrophages with genetically or pharmacologically varied cholesterol and 25HC, to compare and quantify the ingestion of different bacteria, fungi and particles. This project will also address the link between cholesterol synthesis, its storage in lipid bodies and its availability for phagocytosis, based on preliminary data showing such defects in the staggerer mouse model. Notably, cholesterol dysregulation is now a prevalent condition in society and our results will reveal at a fundamental, molecular level how this might compromise immune defenses.Read moreRead less
A role for the actin cytoskeleton in suppression of prion pathology in yeast. The discovery that proteins as well as DNA carry genetic information is leading to a re-think of the mechanisms that program cell behaviour. There is a link between proteins that suppress cancer and protein inheritance. This project explores how heritable changes in proteins control cell behaviour and the implications of this for the origin of cancer.
Expression and substrate recognition by MARCH ubiquitin ligases. Eukaryotic cells are compartmentalised, with different organelles playing distinct functions. This project will characterise the MARCHs, proteins which control the localisation and half-life of other proteins. Understanding how the MARCHs work will provide novel insights into fundamental cellular processes that play major roles in many biological functions.
Subcellular Trafficking Of P Proteins Of Human Pathogenic Viruses: Roles In Viral Pathogenicity And Targeting For Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$578,352.00
Summary
In order to infect humans, pathogenic viruses such as rabies, Nipah, Hendra and Australian bat lyssavirus must be able to evade the immune response. To do this, viruses produce "interferon antagonists" that interfere with specific immune processes by mechanisms that are not fully understood. Our study will characterise the mechanisms used by rabies and other viruses to block immunity, and identify strategies to disable viral immune evasion, rendering these lethal viruses susceptible to destructi ....In order to infect humans, pathogenic viruses such as rabies, Nipah, Hendra and Australian bat lyssavirus must be able to evade the immune response. To do this, viruses produce "interferon antagonists" that interfere with specific immune processes by mechanisms that are not fully understood. Our study will characterise the mechanisms used by rabies and other viruses to block immunity, and identify strategies to disable viral immune evasion, rendering these lethal viruses susceptible to destruction by the human immune system.Read moreRead less
Autophagy: A New Pathway For Presenting Antigen In Dendritic Cells.
Funder
National Health and Medical Research Council
Funding Amount
$444,973.00
Summary
Microbes are chopped up and digested before being displayed to the immune system. Here we will investigate a new pathway termed _autophagy� that helps cells to digest material for immune display.
I am a cell biologist investigating the means by which intracellular compartmentalization of signalling proteins determines signalling outcomes and cell fate. I focus particularly on signals that regulate immune function and cancer progression.
The Role Of Intracellular Protein Trafficking In Alzheimer's Disease
Funder
National Health and Medical Research Council
Summary
Alzheimer’s disease (AD) is a progressive neurological disorder and is the most common cause of dementia. The development of therapies must be preceded by a thorough understanding of the molecular processes that underpin the disease. In this project we will examine the interactions between the Alzheimer’s precursor protein (APP) and the molecular machinery that controls its intracellular localization and breakdown to the toxic A? peptide that is central to disease pathology.
Understanding the basic biology of cells will allow us to pinpoint key mechanisms and molecules that underpin multiple diseases and are targets for treatments. The broad aims of this research program include the development of new therapies for chronic inflammatory diseases, understanding how proteins are sorted and trafficked inside cells in processes that are essential to immunity and cancer biology, and identifying new intracellular targets to block bacterial invasion and infectious diseases.
How membrane-sensing proteins regulate synaptic vesicle endocytosis. This project aims to elucidate the molecular basis of how membrane-sensing proteins regulate synaptic vesicle endocytosis in mammalian central neurons. Nerve cells’ ability to transmit cellular information to one another is important for normal brain function. Efficient communication between neurons through sustained neurotransmitter release relies on the continuous supply of synaptic vesicles in presynaptic nerve terminals. Ke ....How membrane-sensing proteins regulate synaptic vesicle endocytosis. This project aims to elucidate the molecular basis of how membrane-sensing proteins regulate synaptic vesicle endocytosis in mammalian central neurons. Nerve cells’ ability to transmit cellular information to one another is important for normal brain function. Efficient communication between neurons through sustained neurotransmitter release relies on the continuous supply of synaptic vesicles in presynaptic nerve terminals. Key to this process are membrane dynamics during synaptic vesicle retrieval, but the precise underlying mechanisms are not well understood. The intended outcome of this project is insights into the molecular mechanisms of synaptic transmission, the fundamental process of brain function, increasing understanding of physiological processes such as muscle movement, vision, hearing, touch, learning and memory.Read moreRead less